MICROENCAPSULATED CILIARY NEUROTROPHIC FACTOR - PHYSICAL-PROPERTIES AND BIOLOGICAL-ACTIVITIES

Controlled drug release in the CNS and PNS is still an obstacle to the treatment of neurodegenerative disorders. We have prepared a variety of microspheres containing either ciliary neurotrophic factor (CNTF) o r genetically engineered cells able to synthesize and release this cyt okine. CNTF is a multifunctional cytokine that can regulate the surviv al and differentiation of many types of developing and adult neurons. However, when given in therapeutically effective doses by systemic inj ections, it produces numerous adverse side effects. In order to minimi ze these effects we have microencapsulated it in biopolymers (chitosan s, alginates, and copolymers in various proportions to achieve differe nt kinetic properties). Size distribution profiles were determined by an image analysis system and surface characteristics were assessed by electron microscopy. The total content of CNTF as well as the amounts released per day were determined by ELISA and in vitro bioassays. The results from the release kinetics demonstrate that long-term secretion (up to 24 days) of CNTF is achieved by combining chitosan with copoly merized lactic and glycolic acid, whereas microspheres made of alginat e provided only relatively short-term release (2-12 days). Neuron surv ival and neurite outgrowth in cultures of ciliary ganglia were support ed by microencapsulated CNTF, indicating biological stability of CNTF. Genetically engineered human kidney cells 293 continued synthesizing CNTF within spheres and the released amounts of CNTF in the culture me dium were comparable to the amounts secreted from monolayers (1 ng/ml of supernatant from confluent cultures) or even higher. These studies provide a basis for future testing of CNTF in encapsulated preparation s using animal models of neurodegenerative disorders. (C) 1996 Academi c Press, Inc.